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      Efficacy of Caspofungin in Unclassified Invasive Fungal Infection Cases: A Retrospective Analysis of Patients with Hematological Malignancies in China

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          Abstract

          Background

          The management of invasive fungal infection (IFI) is challenging in immunocompromised patients who do not fully satisfy the EORTC/MSG diagnostic criteria of proven or probable IFI. Our study assessed caspofungin efficacy in 582 Chinese patients with hematological malignancies exhibiting unclassified signs or symptoms of IFI.

          Material/Methods

          This retrospective study included caspofungin treatment outcomes of an unclassified group A (n=401) of patients without microbiological or biomarker results and group B (n=181) patients with positive microbiological or biomarker results. Factors that correlated with clinical outcomes were determined using univariate and multivariate analyses.

          Results

          Cough (41.8%), expectoration (29.6%), and chest tightness (14.6%) were the most common clinical features, and changes in CT images (88.1%) were more frequently detected than in X-ray images (19.6%) in all patients. Favorable response rates for caspofungin as first-line treatment were 58.2% for group A and 56.3% for group B. Eastern Cooperative Oncology Group (ECOG) score, cardiovascular disease, hemoptysis, and absolute neutrophil count (ANC) <1000/mm 3 before antifungal treatment without recovery were associated with unfavorable clinical outcome ( P<0.05 for all). Cough and ANC recovery >1000/mm 3 were significantly associated with favorable (complete or partial resolution) outcome.

          Conclusions

          Caspofungin was effective for treating unclassified IFIs of immunocompromised patients. Cardiovascular disease, ECOG score, cough, and/or hemoptysis, as well as ANC count, represent a potential index for estimating response of unclassified IFI patients to caspofungin treatments.

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          Most cited references23

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          Aspergillosis case-fatality rate: systematic review of the literature.

          To update the case-fatality rate (CFR) associated with invasive aspergillosis according to underlying conditions, site of infection, and antifungal therapy, data were systematically reviewed and pooled from clinical trials, cohort or case-control studies, and case series of >/=10 patients with definite or probable aspergillosis. Subjects were 1941 patients described in studies published after 1995 that provided sufficient outcome data; cases included were identified by MEDLINE and EMBASE searches. The main outcome measure was the CFR. Fifty of 222 studies met the inclusion criteria. The overall CFR was 58%, and the CFR was highest for bone marrow transplant recipients (86.7%) and for patients with central nervous system or disseminated aspergillosis (88.1%). Amphotericin B deoxycholate and lipid formulations of amphotericin B failed to prevent death in one-half to two-thirds of patients. Mortality is high despite improvements in diagnosis and despite the advent of newer formulations of amphotericin B. Underlying patient conditions and the site of infection remain important prognostic factors.
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            Delaying amphotericin B-based frontline therapy significantly increases mortality among patients with hematologic malignancy who have zygomycosis.

            Zygomycosis is an emerging opportunistic mycosis among immunocompromised patients with a particularly poor prognosis. We analyzed the impact of delaying effective amphotericin B-based therapy on outcome among 70 consecutive patients with hematologic malignancy who had zygomycosis in our institution during the period 1989-2006. We used classification and regression tree analysis to identify the mortality breakpoint between early and delayed treatment. Delayed amphotericin B-based therapy (i.e., initiating treatment >/=6 days after diagnosis) resulted in a 2-fold increase in mortality rate at 12 weeks after diagnosis, compared with early treatment (82.9% vs. 48.6%); this remained constant across the years of the study and was an independent predictor of poor outcome (odds ratio, 8.1; 95% confidence interval, 1.7-38.2; P = .008) in multivariate analysis. Active malignancy (P = .003) and monocytopenia (P =.01) at the time of diagnosis of infection were also independently associated with a poor outcome, whereas salvage posaconazole-based therapy (P=.01) and neutrophil recovery (P = .009) were predictive of a favorable outcome. Because discriminating between zygomycosis and aspergillosis in a timely fashion is difficult, the pursuit of aggressive diagnostic strategies and prompt initiation of antifungal agents with activity against Zygomycetes should be considered for patients with hematological malignancy who are at an increased risk for zygomycosis.
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              A prospective observational study of candidemia: epidemiology, therapy, and influences on mortality in hospitalized adult and pediatric patients.

              We conducted a prospective, multicenter observational study of adults (n=1447) and children (n=144) with candidemia at tertiary care centers in the United States in parallel with a candidemia treatment trial that included nonneutropenic adults. Candida albicans was the most common bloodstream isolate recovered from adults and children (45% vs. 49%) and was associated with high mortality (47% among adults vs. 29% among children). Three-month survival was better among children than among adults (76% vs. 54%; P<.001). Most children received amphotericin B as initial therapy, whereas most adults received fluconazole. In adults, Candida parapsilosis fungemia was associated with lower mortality than was non-parapsilosis candidemia (24% vs. 46%; P<.001). Mortality was similar among subjects with Candida glabrata or non-glabrata candidemia; mortality was also similar among subjects with C. glabrata candidemia who received fluconazole rather than other antifungal therapy. Subjects in the observational cohort had higher Acute Physiology and Chronic Health Evaluation II scores than did participants in the clinical trial (18.6 vs. 16.1), which suggests that the former subjects are more often excluded from therapeutic trials.
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                Author and article information

                Journal
                Med Sci Monit
                Med. Sci. Monit
                Medical Science Monitor
                Medical Science Monitor : International Medical Journal of Experimental and Clinical Research
                International Scientific Literature, Inc.
                1234-1010
                1643-3750
                2018
                29 July 2018
                : 24
                : 5258-5270
                Affiliations
                [1 ]Department of Hematology, Peking University People’s Hospital, Beijing, P.R. China
                [2 ]Department of Hematology, Ruijin Hospital Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China
                [3 ]Department of Hematology, Union Hospital Tongji Medical College Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China
                [4 ]Department of Hematology, First Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang, P.R. China
                [5 ]Department of Hematology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China
                [6 ]Department of Hematology, Nanfang Hospital, Guangzhou, Guangzhou, Guangdong, P.R. China
                [7 ]Department of Hematology, Tianjin Medical University General Hospital, Tianjin, P.R. China
                [8 ]Department of Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, P.R. China
                [9 ]Department of Hematology, Chinese PLA General Hospital, Beijing, P.R. China
                [10 ]Department of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P.R. China
                Author notes
                Corresponding Author: Xiaojun Huang, e-mail: huangxiaojun@ 123456bjmu.edu.cn
                [A]

                Study Design

                [B]

                Data Collection

                [C]

                Statistical Analysis

                [D]

                Data Interpretation

                [E]

                Manuscript Preparation

                [F]

                Literature Search

                [G]

                Funds Collection

                Article
                908831
                10.12659/MSM.908831
                6080585
                30056458
                8519b6b9-3635-49c6-a34a-862493548ad5
                © Med Sci Monit, 2018

                This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International ( CC BY-NC-ND 4.0)

                History
                : 05 January 2018
                : 03 April 2018
                Categories
                Clinical Research

                antifungal agents,fruiting bodies, fungal,hematologic neoplasms

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